全文获取类型
收费全文 | 834篇 |
免费 | 59篇 |
出版年
2023年 | 3篇 |
2022年 | 6篇 |
2021年 | 22篇 |
2020年 | 17篇 |
2019年 | 9篇 |
2018年 | 22篇 |
2017年 | 17篇 |
2016年 | 31篇 |
2015年 | 38篇 |
2014年 | 41篇 |
2013年 | 69篇 |
2012年 | 66篇 |
2011年 | 76篇 |
2010年 | 29篇 |
2009年 | 29篇 |
2008年 | 56篇 |
2007年 | 46篇 |
2006年 | 28篇 |
2005年 | 35篇 |
2004年 | 43篇 |
2003年 | 40篇 |
2002年 | 34篇 |
2001年 | 14篇 |
2000年 | 6篇 |
1999年 | 9篇 |
1998年 | 3篇 |
1997年 | 4篇 |
1996年 | 5篇 |
1995年 | 4篇 |
1994年 | 3篇 |
1993年 | 3篇 |
1992年 | 6篇 |
1991年 | 7篇 |
1990年 | 6篇 |
1988年 | 3篇 |
1987年 | 4篇 |
1986年 | 10篇 |
1985年 | 5篇 |
1984年 | 10篇 |
1983年 | 6篇 |
1981年 | 3篇 |
1980年 | 4篇 |
1979年 | 4篇 |
1978年 | 2篇 |
1969年 | 1篇 |
1968年 | 1篇 |
1967年 | 1篇 |
1965年 | 2篇 |
1960年 | 1篇 |
1959年 | 2篇 |
排序方式: 共有893条查询结果,搜索用时 62 毫秒
1.
Anu Lipsanen Stefanie Flunkert Kristina Kuptsova Mikko Hiltunen Manfred Windisch Birgit Hutter-Paier Jukka Jolkkonen 《PloS one》2013,8(3)
Experimental studies have identified a complex link between neurodegeneration, β-amyloid (Aβ) and calcium homeostasis. Here we asked whether early phase β-amyloid pathology in transgenic hAPPSL mice exaggerates the ischemic lesion and remote secondary pathology in the thalamus, and whether a non-selective calcium channel blocker reduces these pathologies. Transgenic hAPPSL (n = 33) and non-transgenic (n = 30) male mice (4–5 months) were subjected to unilateral cortical photothrombosis and treated with the non-selective calcium channel blocker bepridil (50 mg/kg, p.o., once a day) or vehicle for 28 days, starting administration 2 days after the operation. Animals were then perfused for histological analysis of infarct size, Aβ and calcium accumulation in the thalamus. Cortical photothrombosis resulted in a small infarct, which was associated with atypical Aβ and calcium accumulation in the ipsilateral thalamus. Transgenic mice had significantly smaller infarct volumes than non-transgenic littermates (P<0.05) and ischemia-induced rodent Aβ accumulation in the thalamus was lower in transgenic mice compared to non-transgenic mice (P<0.01). Bepridil decreased calcium load in the thalamus (P<0.01). The present data suggest less pronounced primary and secondary pathology in hAPPSL transgenic mice after ischemic cortical injury. Bepridil particularly decreased calcium pathology in the thalamus following ischemia. 相似文献
2.
J C Galleyrand P Fulcrand J P Bali M Rodriguez R Magous J Laur J Martinez 《Peptides》1992,13(3):519-525
Binding to gastrin receptors and gastric acid secretion experiments were performed with gastrin derivatives modified at the C-terminal tetrapeptide amide from HG-13 sequence. 1. When the ultimate phenylalanine amide was replaced by a phenethylester or a phenetylamide moiety, the resulting compound bound to gastrin receptors (Kd approximately 10 nM) and exhibited antagonist activity on gastrin-induced acid secretion in the anesthetized rat. 2. Changing the peptide bond between Trp and Leu residues to a -omega(CH2-NH)- bond resulted in a compound which also bound to gastrin receptors (Kd approximately 10 nM) but presented agonist activity on acid secretion in the rat. In contrast, when the peptide bond between Leu and Asp residues was replaced by a -omega(CH2-NH)- bond, the resulting compound was devoid of any affinity for gastrin receptor (Kd greater than 10(-6) M) and of any biological activity. 3. The HG-13 derivatives were synthesized in sulfated and unsulfated forms: O-sulfation of the HG-13 tyrosine residue did not change its intrinsic in vivo activity but enhanced its affinity for gastrin receptors (Kd approximately 0.3 nM). On the contrary, O-sulfation of the various chemically modified HG-13 had no significant effect in either in vitro or in vivo experiments. 4. Finally, no significant difference between binding on parietal (F3) and nonparietal (F1) cells was observed, in agreement with the presence of a gastrin-type receptor in these two cell populations. 相似文献
3.
Muscarinic stimulation of inositol phosphate accumulation and acid secretion in gastric fundic mucosal cells 总被引:1,自引:0,他引:1
The muscarinic agonist, carbachol (CCh), was shown to stimulate the production of inositol phosphates (IP) in isolated cells from rabbit fundic mucosa. This stimulatory effect was time- and dose-dependent: EC50 values for IP1, IP2 and IP3 accumulation were not statistically different. The mean value was 30 +/- 8 microM (n = 6). The corresponding maximal stimulation (% of basal value) observed after 20 min incubation in the presence of 100 microM CCh was 160 +/- 15%. CCh-induced IP accumulation was abolished by atropine (Ki = 0.32 +/- 0.18 nM (n = 3)). The CCh concentrations leading to half-maximal inhibition of N-[3H]methylscopolamine binding and half-maximal IP accumulation were similar. The half-maximal value for CCh-induced aminopyrine accumulation was 8-times lower. These results indicate that IP3-mediated mobilization of intracellular Ca2+ might be involved in CCh-induced acid secretion by parietal cells. 相似文献
4.
The aspartic acid residue at the penultimate position is known to be essential for the hormonal activity of CCK and gastrin on gastric acid secretion. This residue was successively replaced by beta-aspartic acid, beta-alanine, and glutamic acid in the C-terminal heptapeptide of CCK 27-33. The analogues obtained were tested on rat gastric acid secretion and for recognition by gastrin receptors. The replacement by beta-aspartic or beta-alanine decreased gastric secretion and gastrin receptor recognition. In contrast, replacement by glutamic acid affected these two parameters less. The nature of the N-blocking group (Boc or Z) also influenced these activities, Boc derivatives being more potent than Z derivatives. The results were compared to those previously obtained on pancreatic secretion and on stimulation of gall bladder contraction where the modifications were found capable of differentiating between cholecystokinin, pancreozymin and gastrin activities. 相似文献
5.
Lymphoid cell subclasses in rejecting renal allograft in the rat 总被引:4,自引:0,他引:4
We have quantitated the frequency of lymphoid cell subsets in rejecting renal allografts and in the spleen of the allograft recipient during drug-unmodified rejection in the rat. The number of inflammatory (white) cells in the graft was approximately similar to the number of white cells responding to the allograft in the recipient spleen. The inflammatory population of the graft consisted of lymphoid cells and mononuclear phagocytes, with increasing numbers of macrophages toward the end of rejection. Analysis of allograft cellular dispersates with monoclonal antibodies directed to the lymphoid cell subsets demonstrated that although the majority of allograft-infiltrating lymphocytes were T cells, a sizable B-cell proliferation and immunoglobulin synthesis was associated with the inflammatory response of rejection. Within the T-cell subset, the T suppressor/killer cells predominated in the graft whereas the predominant lymphoid cell subset responding to the allograft in the recipient spleen was the T helper cell. 相似文献
6.
In order to find a suitable reagent for extracting the muscarinic receptor from rat brain membranes 14 different detergents
were tested. Only the plant glycoside digitonin efficiently solubilized the receptor protein in its native form. At the same
time microviscosity of detergent micelles was determined by measuring the fluorescence polarization of a hydrophobic fluorescent
probe diphenylhexatriene incorporated into the micelles. In the case of digitonin the polarization value was close to the
corresponding value obtained for rat brain membrane fragments, while for the other detergents studied it remained considerably
lower. The results obtained indicate that the fluidity of detergent micelles may play an important role in retaining the active
conformation of the solubilized muscarinic receptor. 相似文献
7.
Effects of SO2, aqueous fluoride (NaF) and a solution of nitrogen compounds (NH4NO3) on the visible symptoms, pollutant accumulation and ultrastructure of Scots pine (Pinus sylvestris L.) and Norway spruce [Picea abies (L.) Karst.] seedlings were studied in an open-air experiment lasting for 3 consecutive years. Visible injury symptoms were
most pronounced in combination exposures and whenever F was applied. Visible symptoms correlated well with needle pollutant
concentrations. Exposure to NaF increased needle F contents particularly when F was applied with SO2 or NH4NO3. This suggests that a reduction in N or SO2 emissions, in F polluted areas, could improve the condition of conifers via decreased accumulation of phytotoxic F in the
needles. Norway spruce needles accumulated 2 – 10 times as much S and F as those of Scots pine. Microscopic observations showed
various changes in the needle mesophyll cell ultrastructure. In both species, exposure to SO2 increased significantly the amount of cytoplasmic vacuoles, suggesting detoxification of excess sulphate or low pH. F treatments
resulted in a significant enlargement of plastoglobuli in Scots pine and a darkening of plastoglobuli in Norway spruce. All
exposures enhanced the accumulation of lipid bodies. An increased portion of translucent plastoglobuli was most pronounced
in N treatments. Many of the ultrastructural changes and visible symptoms appeared only as number of years exposed increased,
indicating that long-term experiments are needed. Both visible symptoms and ultrastructural changes pointed to the more pronounced
sensitivity of Norway spruce compared to Scots pine. Ultrastructural results mostly supported earlier qualitative observations
of F, N and SO2 effects on needle mesophyll cell ultrastructure. However, no reduction of thylakoids in SO2 containing exposure or curling of thylakoids in F exposure could be detected in the present study.
Received: 5 December 1994 / Accepted: 28 April 1995 相似文献
8.
Extracelluar lipase activity was detected in a culture of Pseudomonas strain Ptm+ growing on hexachlorocyclohexane. Lipase activity was associated with growth of the bacterium and reached a peak at early idiophase (22 h). Following the lipase activity, bioemulsifier was produced, with maximum activity at mid-idiophase (32 h). The extracellular lipase is probably involved in the extracellular synthesis of the bioemulsifier in the culture broth. 相似文献
9.
A complete synthesis of 1-O-hexadecyl-2-O-N-(heptadec-8-cis-enyl)carbamyl-sn-glycero-3-Phosphocholine, a novel analog of phosphatidylcholine, has been described. Each step is simple to perform and gives the desired products in high yield. Also, some of the intermediates formed during the synthesis have been efficiently utilized to prepare 1-O-hexadecyl-2-O-oleyl-sn-glycero-3-phosphocholine, 1-O-hexadecyl-2-oleoyl-sn-glycero-3-phosphochloine and 3-O-hexadecyl-2-oeloyl-sn-glycero-1-phosphocholine. These phosphatidylcholine (PC) analogs are useful for studying the possible role of phospholipases in the capture and lyses of liposomes in vivo. 相似文献
10.
The hexapeptide Z-Tyr(SO-3)-Met-Gly-Trp-Met-Asp-NH2, from the natural sequence of C-terminal cholecystokinin was found to be a competitive antagonist of cholecystokinin receptors, in vitro. In the present study, we report that this peptide inhibits gastrin-induced acid secretion in vivo, (ED50 = 1.5 mumol . kg-1), without agonist activity. Desulfation of the tyrosine residue slightly altered this effect. The tripeptide Boc-Trp-Met-Asp-NH2 showed similar effects, but had lower potency (ED50 = 12 mumol . kg-1). From these preliminary results, it can be concluded that removal of the phenylalanine residue from the C-terminal sequence of CCK or gastrin, leads to an antagonist of the natural hormones and that C-terminal phenylalanine residue is important for agonist activity. As compared with proglumide, a well known gastrin receptor antagonist, these peptides were 20-200 times more potent as inhibitors on the same model. 相似文献